Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease

Szodoray, Péter; Nakken, Britt; Baráth, Sándor; Gaál, János; Aleksza, Magdolna; Zeher, Margit; Sipka, Sándor; Szilagyi, Anna; Zöld, Éva; Szegedi, Gyula; Bodolay, Edit

doi:10.1093/intimm/dxn056

Cited by 25 publications

(22 citation statements)

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“…Based on these findings we assume that the regulation of immune responses is defective and the suppressor activity towards autoimmune processes is diminished. Additionally, we have recently reported that nTreg cells have an important controlling role in the development of systemic autoimmune diseases, namely in the transition from the undifferentiated to the definitive CTD stage (6).…”

Section: Discussionmentioning

confidence: 99%

“…In our previous work we revealed the overproduction of interferon (IFN)-g, produced by T-helper (Th)1 cells, and a decreased number of natural CD4+CD25 high Foxp3+ regulatory T cells (nTregs) in patients with UCTD (6). A subset of interleukin (IL)-17-producing helper T cells (Th17 cells) distinct from Th1 or Th2 cells have been shown to play an important role in the induction of tissue inflammation and autoimmunity (7)(8)(9).…”

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confidence: 99%

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Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease

Zöld

Szodoray

Kappelmayer

et al. 2010

Scandinavian Journal of Rheumatology

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease

Zöld

Szodoray

Kappelmayer

et al. 2010

Scandinavian Journal of Rheumatology

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“…In these patients, the assessment of Treg cells showed that the percentage and absolute number of CD4+CD25 bright FoxP3+, natural Tregs were diminished in UCTD patients compared with healthy controls, while the number of CD4+IL-10+, inducible Tregs was increased [18]. This progressive divergent shift in natural and induced T-regulatory cells clearly predicted the transition from the undifferentiated connective tissue disease to a well-established systemic autoimmune disease [18].…”

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confidence: 95%

“…As a natural follow-up to these findings, we previously investigated the regulatory T cell pool of patients with UCTD [18]. In these patients, the assessment of Treg cells showed that the percentage and absolute number of CD4+CD25 bright FoxP3+, natural Tregs were diminished in UCTD patients compared with healthy controls, while the number of CD4+IL-10+, inducible Tregs was increased [18].…”

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confidence: 99%

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Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Nakken

Bodolay

Szodoray

2014

Clinic Rev Allerg Immunol

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Undifferentiated connective tissue disease (UCTD) is a unique clinical entity, a potential forerunner of well-established systemic autoimmune/rheumatic diseases. UCTD is characterized by the presence of various clinical symptoms, as well as a diverse repertoire of autoantibodies, resembling systemic autoimmune diseases. Since approximately one-third of these patients consequently transform into a full-blown systemic autoimmune/rheumatic disease, it is of major importance to assess pathogenic factors leading to this progression. In view of the fact that the serological and clinical picture of UCTD and systemic autoimmune diseases are very similar, it is assumed that analogous pathogenic factors perpetuate both disease entities. In systemic autoimmune conditions a quantitative and qualitative impairment of regulatory T cells have been shown previously and in parallel a relative dominance of proinflammatory Th17 cells has been introduced. Moreover the imbalance between regulatory and Th17 cells plays a pivotal role in the initiation and propagation of UCTD. Additionally, we depict a cytokine imbalance, which give raise to a biased T-cell homeostasis from the UCTD phase throughout the fully developed systemic autoimmune disease stage. The levels of IL-6, IL-12, IL-17, IL-23 and IFN- were pathologically increased with a parallel reduction of IL-10. We believe that the assessment of Th17/Treg cell ratio, as well as the simultaneous quantitation of cytokines may give a useful diagnostic tool at the early UCTD stage to identify patients with a higher chance of consecutive disease progression towards serious systemic autoimmune diseases. Moreover, the early-targeted immunomodulating therapy in these patients may decelerate, or even stop this progression, before the development of serious autoimmune conditions with organ damage.

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Vitamin D and connective tissue diseases

et al. 2020

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Objective and design Recently, many studies have shown that the biologically active form of vitamin D-1,25(OH) 2 D-is involved in many biological processes, including immune system modulation, and patients affected by various autoimmune diseases, such as connective tissue diseases (CTD), showed low levels of vitamin D. It is not clear if vitamin D deficiency is involved in the pathogenesis of autoimmune diseases or it is a consequence. Material We carried out a review of literature to summarize the existing connections between 25-OH vitamin D and CTD. Methods We searched for articles on PubMed by keywords: vitamin D, connective tissue diseases, systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, undifferentiated connective tissue disease. Results The relationship between vitamin D and CTD is still not very clear, despite many studies having been performed and some data suggest a connection between these diseases and 25-OH vitamin D levels. Conclusions The limitations of the study, such as the heterogeneity of patients, methods used to measure vitamin D serum concentration and other biases, do not lead to unequivocal results to demonstrate a direct link between low vitamin D serum levels and autoimmune diseases. Further studies are needed to resolve conflicting results.

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Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease

Cited by 25 publications

References 27 publications

Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease

Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Vitamin D and connective tissue diseases

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